SUMMARY Wide deployment of malaria control tools in the past decade has significantly contributed to substantial reduction of the incidence and deaths related to the disease in Sub-Sahara Africa.. Yet, the region continues to carry a disproportionately high share of the global malaria burden of malaria deaths. Moreover, incidence remains high but stable in some settings while rebounding in others after a long period of decrease associated with intensive deployment of malaria control tools. The Overall goal of this ICEMR is to understand the variable effectiveness of current malaria control interventions in different ecological settings of West Africa through research to understand interactions between the parasite (response to drug treatment, genotypes, gametocyte survival), human (immune response and host genetics) and the vector (ecology, behaviors, and response to insecticides) and regulating influences of the local environment and human behavior. This ICEMR encompasses 3 Projects with the goals summarized as follow: 1] Epidemiology Project (Project 1): The goal is to understand why different patterns of malaria epidemiology and endemicity are resilient to current control strategies at four sites in Mali, representing different eco-zones across West Africa, 2] Malaria immuno- genomics Project (Project 2): The goal of this project is to identify genetic variation in the malaria parasite and human host, and assess the impact of these differences on malaria transmission and effectiveness of malaria control measures in four sites of Mali , 3] Malaria vector and transmission field ecology project (Project 3): The project goal is to investigate important neglected aspects of malaria vector and transmission field ecology at four sites in Mali, representing three eco-zones across West Africa. These projects links the different aspects of malaria transmission and disease into a unified whole, adding the ability to distinguish the contributions of different malaria control interventions on parasite population and range of immune responses (Project 2, Immunopahtogenesis) and seasonal and geographical distribution of anopheline mosquitoes vectors (Project 3). Understanding the factors relating entomological and epidemiological patterns of transmission will provide more definitive guidelines for malaria control efforts in Mali and in West Africa.